Saccharomyces cerevisiae

Intricate, dynamic, and absolutely unavoidable ageing affects cells and organisms through their entire lifetime. Driven by diverse mechanisms all leading to compromised cellular functions and finally to death, this process is a challenge for researchers. The molecular mechanisms, the general rules that it follows, and the complex interplay at a molecular and cellular level are yet little understood. Here, we present our results showing a connection between the linker histones, the higher-order chromatin structures, and the process of chronological lifespan of yeast cells. By deleting the gene for the linker histone in Saccharomyces cerevisiae we have created a model for studying the role of chromatin structures mainly at its most elusive and so far barely understood higher-order levels of compaction in the processes of yeast chronological lifespan. The mutant cells demonstrated controversial features showing slower growth than the wild type combined with better survival during the whole process. The analysis of the global chromatin organization during different time points demonstrated certain loss of the upper levels of chromatin compaction in the cells without linker histone. The results underlay the importance of this histone for the maintenance of the chromatin loop structures during ageing

Nordic Walking: A Tool for Prevention and Rehabilitation Therapy

The phenomenon of Nordic walking first appeared in Finland in the 1980s as a method for skiers to train during the off-season. In recent years, its popularity has grown significantly. It is a highly effective and, at the same time, affordable form of physical activity. It is performed with special devices called sticks, which serve as supports and allow weight redistribution, reduce the load on the joints, and increase muscle strength as all the muscles of the body are loaded. Originally, it was used in the Scandinavian countries, but due to its simplicity and efficiency, it soon gained popularity throughout Europe. Nordic walking is a good health prevention alternative for a wide range of people. Research shows that it can improve the quality of life of both the elderly and people with various diseases.The purpose of this article is to give a scientific view of Nordic walking and its possibilities as a method of prevention and rehabilitation of many diseases.Material and methods: Review and analysis of scientific publications and literature sources found in the following databases: Google Scholar, ResearchGate, PubMed, SportDiscus, and others.Conclusion: Today, Nordic walking is very popular all over the world. There is already a Nordic Walking Federation in many countries, and competitions are held. Nordic walking is a good alternative for a wide range of people for health prevention. Research shows that it can improve the quality of life of both the elderly and be included in the rehabilitation of people with various diseases

Comparative bioavailability of a newly developed Irbesartan 300 mg containing preparation

Introduction: Irbesartan (CAS registry: 138402-11-6) is a potent, orally active, selective antagonist of the angiotensin II receptors (type AT1) indicated for the treatment of arterial hypertension and chronic heart failure. Aim: The objective of the present study was to demonstrate the bioequivalence of an oral test preparation (Irbesartan 300 mg film-coated tablets Tchaikapharma High Quality Medicines Inc., Bulgaria) and a reference (Aprovel 300 mg film-coated tablets, Sanofi Clir SNC, France), by comparing the rate and extent of absorption of both products upon a single oral administration of the tablets under fasting conditions in healthy volunteers. Methodology: The study was carried out as a single-center, open-label, randomised, twoperiod, single dose, crossover oral bioequivalence study in 40 healthy male and female subjects under fasting conditions. During each study period blood samples for analysis of irbesartan were taken prior to dosing and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours after dosing. The separated plasma was analyzed in the bioanalytical division of Anapharm Europe with a validated method using reversed phase high performance liquid chromatography coupled to a tandem mass spectrometry detector (RP-LC/MS/MS). Results: The point estimates with 90% confidence intervals of the geometric mean ratios of test and reference (T/R) in the study were found to be 102.39% (95.55% - 109.71%) for Cmax and 98.56 % (92.72 % - 104.76 %) for AUC0-72. Thus, the corresponding ratios of Cmax and AUC0-72 met the predetermined criteria for bioequivalence (90% confidence intervals of the geometric mean ratios of test and reference within the 80.00% - 125.00%). Both products were generally very well tolerated. Conclusions: Irbesartan 300 mg film-coated tablets, Tchaikapharma High Quality Medicines Inc., Bulgaria) and Aprovel 300 mg film-coated tablets (Sanofi Clir SNC, France), are bioequivalent with regard to the rate and extent of absorption

Insights into antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine affecting the new SARS-CoV-2

Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia with an unusual outbreak in Wuhan, China, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is currently no licensed antiviral treatment available to prevent human CoV infection. The widespread clinical use and existing knowledge on antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine in the treatment of previous epidemic diseases, namely, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), may be helpful in the combat with novel SARS-CoV-2 infection. Recent clinical evidence didn’t confirm the beneficial role of lopinavir/ritonavir and chloroquine/hydroxychloroquine for COVID-19 patients and their use was reassessed. We provide an overview of the current evidence into the mechanisms of action of these available drugs which are repurposed for treatment of the new virus. Available data identifies remdesivir as an adenosine analogue that can target the RNA-dependent RNA polymerase and block viral RNA synthesis. It has been a promising antiviral drug against a wide array of RNA viruses. 3CLpro is a major CoV protease that cleaves the large replicase polyproteins during viral replication and can be targeted by the protease inhibitor lopinavir/ritonavir but the clinical effects are controversial. Chloroquine/Hydroxychloroquine could impair the replication of SARSCoV-2 by multiple mechanisms and their immunomodulatory properties could ameliorate clinical manifestations that are mediated by immune reactions of the host although its beneficial effects are under question and need to be proven at the clinical level. Existing in vitro and in vivo evidence delineate the molecular mechanisms of these drugs in CoV-infected cells. Numerous studies demonstrated the ability of remdesivir to inhibit SARS-CoV-2 replication but future research would be needed to understand the exact mode of action of lopinavir/ritonavir and chloroquine/hydroxychloroquine in SARS-CoV-2 infected cells and to use this knowledge in the treatment of the current COVID-19

Effects of pioglitazone therapy on blood parameters, weight and BMI: a meta-analysis

Abstract Background Type 2 diabetes mellitus (T2DM) is one of the most common diseases worldwide and insulin insufficiency and insulin resistance are two main metabolic issues connected with it. The dyslipidemia associated with insulin resistance and T2DM is characterized by higher triglycerides (TGs), higher very-low-density lipoprotein cholesterol and lower apo A1. Pioglitazone, a member of the thiazolidinedione class, with a proven antihyperglycemic effect, is known to positively influence insulin sensitivity and β-cell function and to have the potential to alter the lipid profile. Methods The aim of our meta-analysis is to summarize and determine the influence of pioglitazone on the glycemic profile and lipoprotein metabolism as well as on weight and BMI in order to highlight the benefit of pioglitazone therapy in patients with T2DM. A comprehensive literature search was conducted through the electronic databases PubMed, MEDLINE, Scopus, PsyInfo, eLIBRARY.ru (from 2000 until February 2016) to identify studies that investigate the effect of pioglitazone on the glycemic and lipid profile and on the weight and BMI. We chose the random-effects method as the primary analysis. Forest plots depict estimated results from the studies included in the analysis and funnel plots are used to evaluate publication bias. Sensitivity analyses were performed in order to evaluate the degree of influence of the consequent elimination of each individual study on the final result. Results Of the 1536 identified sources only 15 randomised trials were included in the meta-analysis. Pioglitazone treatment was associated with improvement in the glycemic profile. It reduced FPG levels by a mean of 1.1–2 mmol/l and HbA1c by a mean of 0.9–1.3%. Our results reaffirmed the hypothesis that pioglitazone has a positive influence on the lipid profile of T2DM patients with increase in TC and HDL, no significant changes in LDL and notable decrease in TGs. Results also showed that pioglitazone therapy led to increase in both weight and BMI (WMD 1.755, 95% CI 0.674 to 2.837 and 1.145, 95% CI 0.389 to 1.901 respectively). Conclusion Our results prove that the PPAR γ agonist pioglitazone has the potential to be beneficial to patients with T2DM

MOESM1 of Effects of pioglitazone therapy on blood parameters, weight and BMI: a meta-analysis

Additional file 1: Figure S1. Funnel plot for FPG. Figure S2. Funnel lot for HbA1c. Figure S3. Funnel plot for total cholesterol. Figure S4. Funnel plot for LDL. Figure S5. Funnel plot for HDL. Figure S6. Funnel plot for TGs. Figure S7. Funnel plot for weight. Figure S8. Funnel plot for BMI

Pioglitazone and the Risk of Bladder Cancer: A Meta-Analysis

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Insights into antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine affecting the new SARS-CoV-2

Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia with an unusual outbreak in Wuhan, China, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is currently no licensed antiviral treatment available to prevent human CoV infection. The widespread clinical use and existing knowledge on antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine in the treatment of previous epidemic diseases, namely, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), may be helpful in the combat with novel SARS-CoV-2 infection. Recent clinical evidence didn’t confirm the beneficial role of lopinavir/ritonavir and chloroquine/hydroxychloroquine for COVID-19 patients and their use was reassessed. We provide an overview of the current evidence into the mechanisms of action of these available drugs which are repurposed for treatment of the new virus. Available data identifies remdesivir as an adenosine analogue that can target the RNA-dependent RNA polymerase and block viral RNA synthesis. It has been a promising antiviral drug against a wide array of RNA viruses. 3CLpro is a major CoV protease that cleaves the large replicase polyproteins during viral replication and can be targeted by the protease inhibitor lopinavir/ritonavir but the clinical effects are controversial. Chloroquine/Hydroxychloroquine could impair the replication of SARSCoV-2 by multiple mechanisms and their immunomodulatory properties could ameliorate clinical manifestations that are mediated by immune reactions of the host although its beneficial effects are under question and need to be proven at the clinical level. Existing in vitro and in vivo evidence delineate the molecular mechanisms of these drugs in CoV-infected cells. Numerous studies demonstrated the ability of remdesivir to inhibit SARS-CoV-2 replication but future research would be needed to understand the exact mode of action of lopinavir/ritonavir and chloroquine/hydroxychloroquine in SARS-CoV-2 infected cells and to use this knowledge in the treatment of the current COVID-19